MONSTER PHASE OF ACETAMINOPHEN USE IN PREGNANCY: CURRENT VISION OF AN OLD DRUG

In various countries, Acetaminophen [APAP] is the frequently used painkiller found in hundreds of medications during pregnancy. It has been broadly used for eras and health care professionals prefer acetaminophen as a choice during pregnancy for relieving pain and fever. Current research reports bothersome inclinations in the rate of acetaminophen exposure and related pregnancy outcome. The exposure of pregnant women to acetaminophen is of great concern. Existing literature evidence shows that acetaminophen exposure during pregnancy may leads to preterm birth, attention deficit hyperactivity disorder (ADHD), autism, male infertility, asthma in pediatrics. Therefore, the prophylactic anticipation of acetaminophen exposure can be a far-sighted approach in order to safeguard humans and wildlife from enduring dangerous effects. This article reviews the epidemiological findings and aims to shed awareness into the second generation outcome of an old drug in pregnant women

Drug resistance among extrapulmonary TB patients: Six years experience from a supranational reference laboratory.

BACKGROUND & OBJECTIVES There is limited information available about the drug resistance patterns in extrapulmonary tuberculosis (EPTB), especially from high burden countries. This may be due to difficulty in obtaining extrapulmonary specimens and limited facilities for drug susceptibility testing. This study was undertaken to review and report the first and second-line anti-TB drug susceptibility patterns in extrapulmonary specimens received at the National Institute for Research in Tuberculosis (NIRT), Chennai, India, between 2005 and 2012. METHODS Extrapulmonary specimens received from referring hospitals were decontaminated and cultured using standard procedures. Drug susceptibility testing (DST) for Mycobacterium tuberculosis was done by absolute concentration or resistance ratio methods for the first and the second line anti-TB drugs. RESULTS Between 2005 and 2012, of the 1295 extrapulmonary specimens, 189 grew M. tuberculosis, 37 (19%) cases were multidrug resistant (MDR) while one was extensively drug resistant (XDR). Specimen-wise MDR prevalence was found to be: CSF-10 per cent, urine-6 per cent, fluids and aspirates-27 per cent, pus-23 per cent, lymph nodes-19 per cent. Resistance to isoniazid and ethionamide was found to be high (31 and 38%, respectively). INTERPRETATION & CONCLUSIONS Drug resistance including MDR-TB was observed in a significant proportion of extrapulmonary specimens referred for DST. Access to culture and DST for extrapulmonary specimens should be expanded. Guidelines for MDR-TB management should have explicit sections on extra-pulmonary tuberculosis and training on laboratory techniques is urgently required

Design, synthesis, characterization and in vitro evaluation of some novel thiol-substituted 1,3,4-oxadiazoles as GlmS inhibitors

The development of novel medications with previously unidentified action mechanisms is required due to the increasing in antibiotic resistance amongst dangerous microbes. The major goal of the research was to develop in silico and in vitro antibacterial methods for designing an active thiol substituted oxadiazole inhibitor targeting gram-negative and gram-positive bacteria's GlmS receptor. 1,3,4-Oxadiazole was proposed as a scaffold, and the possibility of its synthesis was examined. The least amount of free energy in the ligand configurations was chosen. Analyses of the novel molecules' characteristics were done using ADMET studies. There were four distinct reactions used in the synthesis processes. As the first reagent, substituted carboxylic acids were utilized. Synthesized compounds were characterized by spectral studies and minimum inhibitory concentration was evaluated by in vitro antibacterial examinations of synthesized compounds. Ciprofloxacin served as the study's reference drug. Based on in vitro studies and in silico molecular docking, ROS1-4 established strong binding energy, while ROS3 revealed significant antibacterial activity. These findings support the hypothesis that the proposed scaffold significantly inhibits the GlmS receptor protein

Prevalence of Tobacco Use in Urban, Semi Urban and Rural Areas in and around Chennai City, India

BACKGROUND: Tobacco use leads to many health complications and is a risk factor for the occurrence of cardio vascular diseases, lung and oral cancers, chronic bronchitis etc. Almost 6 million people die from tobacco-related causes every year. This study was conducted to measure the prevalence of tobacco use in three different areas around Chennai city, south India. METHODS: A survey of 7510 individuals aged > = 15 years was undertaken covering Chennai city (urban), Ambattur (semi-urban) and Sriperumbudur (rural) taluk. Details on tobacco use were collected using a questionnaire adapted from both Global Youth Tobacco Survey and Global Adults Tobacco Survey. RESULTS: The overall prevalence of tobacco use was significantly higher in the rural (23.7%) compared to semi-urban (20.9%) and urban (19.4%) areas (P value <0.001) Tobacco smoking prevalence was 14.3%, 13.9% and 12.4% in rural, semi-urban and urban areas respectively. The corresponding values for smokeless tobacco use were 9.5%, 7.0% and 7.0% respectively. Logistic regression analysis showed that the odds of using tobacco (with smoke or smokeless forms) was significantly higher among males, older individuals, alcoholics, in rural areas and slum localities. Behavioural pattern analysis of current tobacco users led to three groups (1) those who were not reached by family or friends to advice on harmful effects (2) those who were well aware of harmful effects of tobacco and even want to quit and (3) those are exposed to second hand/passive smoking at home and outside. CONCLUSIONS: Tobacco use prevalence was significantly higher in rural areas, slum dwellers, males and older age groups in this region of south India. Women used mainly smokeless tobacco. Tobacco control programmes need to develop strategies to address the different subgroups among tobacco users. Public health facilities need to expand smoking cessation counseling services as well as provide pharmacotherapy where necessary

Acquired rifampicin resistance in thrice-weekly antituberculosis therapy: impact of HIV and antiretroviral therapy

Risk factors for acquired rifampicin resistance (ARR) among tuberculosis patients on thrice-weekly antituberculosis therapy were baseline isoniazid resistance and HIV. Among HIV-infected patients, higher mycobacterial burden and lower CD4 count, but not highly active antiretroviral therapy, were significantly associated with ARR. Background: Risk factors for acquired rifampicin resistance (ARR) in human immunodeficiency virus (HIV)/tuberculosis coinfection, in the highly active antiretroviral therapy (HAART) era, needs evaluation. We studied the impact of HIV and HAART on ARR among patients taking thrice-weekly antituberculosis therapy. Methods: This cross-protocol analysis included patients with newly diagnosed, rifampicin-susceptible pulmonary tuberculosis, with and without HIV, enrolled in clinical trials (who took &#62;80% of medication) at the National Institute for Research in Tuberculosis between 1999 and 2013. All patients received rifampicin and isoniazid for 6 months reinforced with pyrazinamide and ethambutol in the first 2 months, given thrice-weekly throughout the study along with HAART in one of the groups. Outcomes were categorized and multivariate logistic regression analysis performed to identify risk factors for ARR. Results: The per-protocol results included patients with tuberculosis: 246 HIV-uninfected patients (HIV–TB+), 212 HIV patients not on HAART (non-HAART), and 116 HIV-infected patients on HAART. Median CD4 counts of the latter 2 groups were 150 and 93 cells/&#956;L, respectively, and the median viral loads were 147 000 and 266 000 copies/mL, respectively. Compared with HIV–TB+, the relative risks (RRs) for an unfavorable response in the coinfected, non-HAART and HAART groups were 2.1 (95% confidence interval [CI], 1.7–14.8; P&#60;.0001) and 2.1 (95% CI, .9–5.2; P=.3), whereas for ARR, the RRs were 21.1 (95% CI, 2.6–184; P&#60;.001) and 8.2 (95% CI, .6–104; P=.07), respectively. Conclusions: HIV-infected patients with tuberculosis treated with a thrice-weekly antituberculosis regimen are at a higher risk of ARR, compared with HIV-uninfected patients, in the presence of baseline isoniazid resistance. HAART reduces but does not eliminate the risk of ARR

Number of sputum specimens during treatment follow-up of tuberculosis patients: two or one?

SETTING: National Institute for Research in Tuberculosis clinics in Chennai and Madurai, India. OBJECTIVE: To examine the pattern of serial smears (negative-negative [NN], negative-positive [NP], positive-negative [PN], positive-positive [PP]) during treatment follow-up of culture-confirmed new smear-positive tuberculosis (TB) patients, and the proportion of culture-negatives in each category. DESIGN: We reviewed the records and extracted follow-up smear (fluorescent microscopy) and culture (Löwenstein-Jensen) results of patients enrolled in clinical trials from January 2000 to August 2012 and treated with the Category I regimen (2EHRZ(3)/4HR(3)). Data entry and analysis were performed using EpiData. RESULTS: Among 520 patients (176 infected with the human immunodeficiency virus), the proportions of culture-negative patients with NN, discordant (PN or NP) and PP patterns were approximately 98%, 80% and 40%, respectively. The smear-positive culture-negative phenomenon was more frequent in follow-up smear results graded 1+, followed by 2+ and 3+. CONCLUSION: There is justification for discontinuing the examination of second specimens during treatment follow-up among TB patients. However, a positive result on the first smear needs to be confirmed by a second positive result before making clinical management decisions. The World Health Organization may need to reconsider its recommendation on this issue

Plasma chemokines as immune biomarkers for diagnosis of pediatric tuberculosis

Abstract Background Diagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation. Hence, we measured the plasma chemokines as biomarkers for diagnosis of pediatric tuberculosis. Methods We conducted a prospective case control study using children with confirmed, unconfirmed and unlikely TB. Multiplex assay was performed to examine the plasma CC and CXC levels of chemokines. Results Baseline levels of CCL1, CCL3, CXCL1, CXCL2 and CXCL10 were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics curve analysis revealed that CCL1, CXCL1 and CXCL10 could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 80%. In addition, combiROC exhibited more than 90% sensitivity and specificity in distinguishing confirmed and unconfirmed TB from unlikely TB. Finally, classification and regression tree models also offered more than 90% sensitivity and specificity for CCL1 with a cutoff value of 28 pg/ml, which clearly classify active TB from unlikely TB. The levels of CCL1, CXCL1, CXCL2 and CXCL10 exhibited a significant reduction following anti-TB treatment. Conclusion Thus, a baseline chemokine signature of CCL1/CXCL1/CXCL10 could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis